DESCRIPTION (Investigator's Abstract): This research project proposes to investigate the metabolic changes associated with focal brain activation in normal human subjects. More specifically, positron emission tomography (PET) will be used to measure the increases in regional cerebral metabolic rate of oxygen (rCMROz) and regional cerebral metabolic rate of glucose (rCMRglu) induced by specific visual and somatosensory stimulus paradigms designed to activate histochemically distinct areas within the cortex. We hypothesize that the degree of coupling of activation-induced rCMROz increase to activation-induced rCMRglu increase will be heterogeneous across different stimulus conditions. More specifically, we hypothesize that this heterogeneity will be related to the underlying distribution of the oxidative enzyme cytochrome oxidase in the brain areas activated by the particular stimulus condition, with greater coupling associated with cytochrome oxidase- rich areas (reflecting predominantly oxidative glucose. metabolism) and lesser coupling associated with cytochrome oxidase-poor areas (reflecting mostlyglycolytic metabolism). A total of 50 normal subjects will be studied with each individual undergoing an 150-water regional cerebral blood flow/15O-oxygen rCMROz PET scanning session and a PDG rCMRglu PET scanning session'. During Phase I, 30 subjects will be assigned to one of three visual cortex activation paradigms designed to activate primarily cytochrome oxidase- rich areas ("blob" regions), primarily cytochrome oxidase-poor areas ("interblob" regions), and a mix of blob and interblob regions, - respectively. Phase II will involve 20 subjects enrolled in one of two somatosensory cortex stimulus paradigms. The imaging data will be used to calculate the stimulus-induced increases in rCMR02 and rCMRglu. This will allow us to compare the degree of coupling of rCMR02 increase to rCMRglu increase for three visual stimulus conditions which are expected to activate visual cortical areas with Idifferent underlying cytochrome oxidase distributions and to begin an examination of rCMRO - rCMRglu coupling in brain regions outside the visual cortex. This studies findings could extend the basic understanding of the metabolic processes underlying foal brain activation as well as further the understanding and application of functional imaging activation studies.